title: Preconditioning in rat hearts is independent of mitochondrial F1F0 ATPase inhibition.
abstract: Mitochondrial F1F0 adenosinetriphosphatase (ATPase) is responsible for the majority of ATP synthesis during normoxic conditions, but under ischemic conditions it accounts for significant ATP hydrolysis. A previous study showed that preconditioning in isolated rat hearts is mediated by inhibition of this ATPase during ischemia. We tested this hypothesis in our isolated rat heart model of preconditioning. Preconditioning was accomplished by three 5-min periods of global ischemia separated by 5 min of reperfusion. This was followed by 20 min of global ischemia and 30 min of reperfusion. Preconditioning significantly enhanced reperfusion contractile function and reduced lactate dehydrogenase release but paradoxically reduced the time to onset of contracture during global ischemia. Myocardial ATP was depleted at a faster rate during the prolonged ischemia in preconditioned than in sham-treated hearts, which is consistent with the reduced time to contracture. ATP during reperfusion was repleted more rapidly in preconditioned hearts, which is consistent with their enhanced contractile function. Preconditioning significantly reduced lactate accumulation during the prolonged ischemia. We were not able to demonstrate that mitochondrial F1F0 ATPase (measured in submitochondrial particles) was inhibited by preconditioning before or during the prolonged ischemia. The mitochondrial ATPase inhibitor oligomycin significantly conserved ATP during ischemia and increased the time to the onset of contracture, which is consistent with inhibition of the mitochondrial ATPase. Our results show that preconditioning in rat hearts can be independent of mitochondrial ATPase inhibition as well as ATP conservation.
authors.affiliation: Department of Cardiovascular Biochemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Green
authors.forename: H N
authors.initials: HN
authors.lastname: Murray
authors.forename: P G
authors.initials: PG
authors.lastname: Sleph
authors.forename: F L
authors.initials: FL
authors.lastname: Wang
authors.forename: A J
authors.initials: AJ
authors.lastname: Baird
authors.forename: W L
authors.initials: WL
authors.lastname: Rogers
authors.forename: G J
authors.initials: GJ
authors.lastname: Grover
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000201:enzymology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009840:Oligomycins / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D009840:Oligomycins; C048335:oligomycin B; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases